The method of choice for creating monoclonal antibodies has since 1975 been the Kohler-Milstein technique. This technique involved fusing together an established cell line from a mouse tumor with spleen cells from a mouse. The mouse had previously been immunized with the antigen. It was then necessary to select hybrid cells that survived and screen numerous individual cultures in order to find a hybridoma that made the desired antibody.
"Hybridoma" technology, although a major advance, has significant disadvantages. Because the hybrid cells have extra chromosomes, they are sometimes unstable and lost during culture. Thus, many cultures must be screened to be sure of finding surviving cultures. Further, one often has to culture hybridomas for several months before being sure that a stable clone has been recovered. Further, the screening techniques are frequently burdensome and time consuming.
Another newer technique for antibody development is described in W. Huse et al., 246 Science 1275-1281 (1989). In this technique, a bacteria phage lambda vector system is used to express in E. coli a combinatorial library of antibody fragments of mouse antibody repertoire (in vitro). This system still appears to require significant screening. Also, it has been criticized as being so burdensome that further development will be needed to make it practical. H. Bialy, 8 Biotechnology 184 (1990).
Thus, it can be seen that a need still exists for an improved means of developing antibodies.